Outpatient Cardiology

OUTPATIENT CARDIOLOGY
ROBERT L PAGE II, PHARM.D., MSPH, FCCP,
FASHP, FAHA, FASCP, BCPS, CGP
UNIVERSITY OF COLORADO DENVER
SCHOOLS OF PHARMACY AND MEDICINE
AURORA, COLORADO

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Learning Objectives: mal limits. Which one of the following is the best
management of her HF?
A. Continue current regimen.
1. Recommend patient-specific pharmacologic man-
B. Increase enalapril to 20 mg 2 times/day.
agement of chronic heart failure, with an emphasis
C. Initiate metoprolol extended release 12.5 mg/
on mortality-reducing drugs and their target dos-
day.
ages.
D. Initiate digoxin 0.125 mg/day.
2. Develop an appropriate pharmacologic and moni-
toring plan for patients with atrial fibrillation. 4. J.M. is a 65-year-old woman with a history of hyper-
tension and poor drug adherence who presents to her
3. Given a patient with hypertension, outline the opti- primary care physician with dyspnea and markedly
mal pharmacologic management based on practice decreased exercise tolerance. An echocardiogram
guidelines and clinical trial evidence. reveals an LVEF of 65% with considerable diastolic
dysfunction. J.M.'s drugs include nifedipine extended
4. Create an evidence-based drug regimen for a pa-
release 60 mg/day and hydrochlorothiazide 25 mg/
tient with coronary artery disease in both the pres-
day. Her vital signs include HR 98 beats/minute and
ence and absence of stable angina.
BP 128/78 mm Hg. Her lung fields are clear to auscul-
tation, and there is no evidence of systemic conges-
tion. Which one of the following is the best pharma-
cologic management for J.M.?
A. Discontinue nifedipine and initiate diltiazem
Self-Assessment Questions:
240 mg/day.
Answers to these questions may be found at the B. Discontinue hydrochlorothiazide and initiate
end of this chapter. furosemide 40 mg 2 times/day.
C. Initiate digoxin 0.25 mg/day.
D. Add enalapril 5 mg 2 times/day.
2. R.S., a 58-year-old woman with a history of hyper-
tension, coronary artery disease (CAD) (s/p myo-
5. B.W. is a 78-year-old man with a history of hyper-
cardial infarction [MI] 4 months ago), and dyslip-
tension, peripheral arterial disease, reflux disease,
idemia presents to the clinic for follow-up. She is
and atrial fibrillation (AF). His therapy includes as-
without complaints and specifically has no symp-
pirin 325 mg/day, lansoprazole 30 mg every night,
toms of dyspnea or edema. An echocardiogram re-
atenolol 50 mg/day, lisinopril 10 mg/day, and ator-
veals a left ventricular ejection fraction (LVEF) of
vastatin 20 mg/day. His BP is 132/72 mm Hg, and
35%. Her drugs include aspirin 325 mg/day, meto-
HR is 68 beats/minute. Which one of the following
prolol succinate 200 mg/day, and simvastatin 20 mg
is the best therapy for B.W. at this time?
every night. Her vital signs include heart rate (HR)
A. Add diltiazem and warfarin.
58 beats/minute and blood pressure (BP) 138/80
B. Add digoxin and increase lisinopril to 20 mg/
mm Hg. Her lungs are clear, and her laboratory re-
day.
sults are within the reference range. Which one of
C. Discontinue atorvastatin and add warfarin.
the following is the best management of R.S.'s drug
D. Add warfarin and decrease aspirin to 81 mg/
therapy?
day.
A. Continue current therapy.
B. Initiate digoxin 0.125 mg/day.
6. Z.G. is a 61-year-old man with AF, hypertension,
C. Initiate carvedilol 3.125 mg 2 times/day.
and hypercholesterolemia. His drugs include di-
D. Initiate enalapril 5 mg 2 times/day.
goxin 0.25 mg/day, warfarin 5 mg/day, amlodipine
10 mg/day, and pravastatin 20 mg every night. He
3. J.O., a 64-year-old woman with New York Heart
comes to the clinic today with no complaints except
Association (NYHA) class III nonischemic dilated
for palpitations and dyspnea when doing yard work.
cardiomyopathy and an LVEF of 40%, presents to
His vital signs include BP 138/80 mm Hg and HR
the heart failure (HF) clinic for follow-up. She has
72 beats/minute. All laboratory results are within
no complaints. Her drugs include enalapril 10 mg
normal limits; his international normalized ratio
2 times/day, furosemide 40 mg 2 times/day, and
(INR) is 2.4, and his digoxin concentration is 1.1
potassium chloride (KC1) 20 mEq 2 times/day. Her
ng/dL. Which one of the following is the best option
vital signs include BP 130/88 mm Hg and HR 78
to help with Z.G.'s symptoms?
beats/minute. Her laboratory results are within nor-

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A. Add atenolol 50 mg/day.
B. Increase digoxin to 0.5 mg/day.
C. Continue current regimen; advise Z.G. to
avoid activities that cause symptoms.
D. Add verapamil 240 mg/day.
7. R.P. is an 82-year-old African American man with
a history of hypertension, a transient ischemic at-
tack, and gout. His drugs include allopurinol 300
mg/day, nifedipine extended release 60 mg/day, and
aspirin 81 mg/day. His vital signs include BP 145/85
mm Hg and HR 82 beats/minute. Which one of the
following is the best approach to improve R.P.'s BP
control?
A. Add hydrochlorothiazide 50 mg/day.
B. Add ramipril 2.5 mg/day.
C. Add atenolol 50 mg/day.
D. Add diltiazem 240 mg/day.
8. M.L. is a 32-year-old white woman with a history
of type 1 diabetes mellitus and hypertension. She
takes lisinopril 10 mg/day and uses insulin. Dur-
ing her clinic visit, a pregnancy test is performed
to follow up on a positive home pregnancy test the
patient performed. The results confirm a pregnan-
cy. Her BP today is 162/105 mm Hg, and HR is 88
beats/minute. Which one of the following is the best
therapy for her BP at this time?
A. Increase lisinopril to 20 mg/day and add hy-
drochlorothiazide.
B. Add hydralazine.
C. Discontinue lisinopril and begin methyldopa.
D. Discontinue lisinopril and add losartan.
9. You are asked to design a randomized, placebo-
controlled, clinical trial to examine the ability of a
new ACE inhibitor, Trillionapril, versus enalapril,
to reduce coronary events in patients with a Fram-
ingham 10-year risk of cardiovascular events of
more than 20%. The plan is to include 4500 patients
in each group and to monitor them for an average
of 4.8 years. Which one of the following statistical
tests is best for comparing the proportion of cardio-
vascular events in patients receiving Trillionapril
versus enalapril?
A. Analysis of variance.
B. Mann-Whitney U-test.
C. Student unpaired t-test.
D. Chi-square analysis.
70% lesion of the proximal left anterior descending
artery, which was stented, in addition to mild lu-
minal irregularities throughout most other arteries.
Before admission, his drugs were aspirin 81 mg/day
and simvastatin 40 mg every night (past low-density
lipoprotein cholesterol [LDL-C] was 120 mg/dL).
His BP is 135/75 mm Hg, and his HR is 80 beats/
minute. His discharge orders currently include the
following drugs: aspirin 81 mg/day, clopidogrel 75
mg/day for 6 months (to ensure stent patency), sim-
vastatin 80 mg every night, and ezetimibe 10 mg/
day. Is there anything you would like to do differ-
ently regarding his discharge drugs?
A. Discontinue simvastatin plus ezetimibe and
begin atorvastatin 80 mg/day.
B. Discontinue ezetimibe and add gemfibrozil
600 mg 2 times/day.
C. Add ramipril 5 mg/day.
D. Add atenolol 25 mg/day.
10. R.K. is a 67-year-old man with chronic stable an-
gina. He has had worsening chest discomfort with
exercise and has been using his "as-needed" nitro-
glycerin with increasing frequency. His cardiovas-
cular drugs consist of aspirin 325 mg/day, atenolol
100 mg/day, atorvastatin 80 mg/day, and lisinopril
20 mg/day. Today, his BP is 136/80 mm Hg, and
HR is 60 beats/minute. During exercise, his HR
typically increases to about 85 beats/minute. Which
one of the following suggestions to improve his an-
gina symptom control is best?
A. Add amlodipine 10 mg/day.
B. Discontinue atenolol and begin extended-
release nifedipine 90 mg/day.
C. Add clopidogrel 75 mg/day.
D. Add ezetimibe 10 mg/day.

10. J.T. is a 58-year-old man being discharged from the

hospital after undergoing a diagnostic cardiac cath-
eterization when a treadmill test showed some mild
abnormalities. His medical history is notable only
for hypercholesterolemia. The procedure showed a

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Patient Gases
1. L.S. is a 48-year-old woman with alcohol-induced cardiomyopathy. Her most recent LVEF is 20%; her
daily activities are limited by dyspnea and fatigue (NYHA class III). Her medications include lisinopril
20 mg/day, furosemide 40 mg 2 times/day, carvedilol 12.5 mg 2 times/day, spironolactone 25 mg/day, and
digoxin 0.125 mg/day. Her most recent laboratory results include the following: sodium (Na) 140 mEq/L,
K 4.0 mEq/L, CI 105 mEq/L, bicarbonate 26 mEq/L, blood urea nitrogen (BUN) 12 mg/dL, serum creati -
nine (SCr) 0.8 mg/dL, glucose 98 mg/dL, calcium 9.0 mg/dL, phosphorus 2.8 mg/dL, magnesium (Mg) 2.0
mEq/L, and digoxin 0.7 ng/mL. Her vital signs today include BP of 112/70 mm Hg and HR of 68 beats/
minute. Which one of the following is the best approach for maximizing the management of her HF?
A. Increase carvedilol to 25 mg 2 times/day.
B. Increase lisinopril to 40 mg/day.
C. Increase spironolactone to 50 mg/day.
D. Increase digoxin to 0.25 mg/day.

2. J.T. is a 62-year-old man with a history of CAD (MI 3 years ago), hypertension, depression, chronic renal in -
sufficiency (baseline SCr is 2.8 mg/dL), peripheral arterial disease, osteoarthritis, hypothyroidism, and HF
with an LVEF of 25%. His medications include aspirin 81 mg/day, simvastatin 40 mg every night, enalapril
5 mg 2 times/day, metoprolol extended release 50 mg/day, furosemide 80 mg 2 times/day, cilostazol 100 mg
2 times/day, acetaminophen 650 mg 4 times/day, sertraline 100 mg/day, and levothyroxine 0.1 mg/day. His
vital signs include BP 120/70 mm Hg and HR 72 beats/minute. Laboratory results are within normal limits,
except for a SCr of 2.8. Thyroid-stimulating hormone is 2.6 milliunits/L. His HF is stable and considered
NYHA class II. Which one of the following is the best approach for maximizing the management of his
HF?
A. Discontinue metoprolol and begin carvedilol 12.5 mg 2 times/day.
B. Increase enalapril to 10 mg 2 times/day.
C. Add spironolactone 25 mg/day.
D. Add digoxin 0.125 mg/day.

I. HEART FAILURE

A. Background: HF is a complex clinical syndrome that can result from any structural or functional
cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.
1. Systolic dysfunction (decreased EF less than 40%)
a. Impaired wall motion
b. Dilated ventricle
c. Two-thirds attributable to CAD
d. One-third attributable to nonischemic cardiomyopathy
i. Hypertension
ii. Thyroid disease
iii. Valvular disease
iv. Cardiotoxins
(A) Alcohol
(B) Chemotherapeutic agents
(1) Anthracyclines
(2) Cyclophosphamide
(3) 5-Fluorouracil
(4) Trastuzumab
v. Myocarditis
vi. Idiopathic

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2. Diastolic dysfunction (preserved/normal EF)

a. Accounts for about 30% of patients with HF
b. Impaired ventricular relaxation and filling
c. Normal wall motion
d. Most are caused by hypertension and age-related decreases in the elastic properties of the
cardiovascular system.
e. Some are caused by various cardiomyopathies (e.g., restrictive, infiltrative, hypertrophic).
3. Primary symptoms
a. Dyspnea
b. Fatigue
c. Edema
d. Exercise intolerance
4. Stages of HF

Table 1.
Stage Description Patient Population
A At high risk of HF but without structural Patients with hypertension, atherosclerotic
heart disease or symptoms of HF disease, diabetes mellitus, obesity, or metabolic
syndrome OR patients using cardiotoxins or
having a family history of cardiomyopathy
B Structural heart disease but without signs Patients with a previous MI, left ventricular
or symptoms of HF remodeling, or asymptomatic valvular disease
C Structural heart disease with prior or Patients with known structural heart disease
current symptoms of HF and shortness of breath, fatigue, and/or reduced
exercise tolerance
D Refractory HF requiring specialized Patients who have marked symptoms at rest
interventions despite maximal medical therapy (e.g., those
who are recurrently hospitalized or cannot be
safely discharged from the hospital without
specialized interventions)
HF = heart failure; MI = myocardial infarction.

5. New York Heart Association classification of HF

Table 2.
NYHA Functional Class Description
I No limitations in physical activity because of HF symptoms
II Symptoms of HF with normal level of activity
III Marked limitations in physical activity because of HF symptoms
IV Symptoms of HF at rest

HF = heart failure; NYHA = New York Heart Association.

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Left Ventricular Dysfunction

Neurohormonal Activation

• Norepinephrine • Endothelin
• Angiotensin II • TNFα
• Vasopressin • Aldosterone

Heart Kidneys
Blood vessels

• Peripheral vasoconstriction
• Increased demands on
the heart
• Na+/H20 retention
• Increased neurohormonal
activation • Myocardial fibrosis

Figure 1.
H 2 O = water; Na = sodium; TNFα = tumor necrosis factor alpha.

B. Pharmacologic Therapy for Systolic HF

1. Principles of therapy
a. Block the compensatory neurohormonal activation caused by decreased card iac output
that promotes further cardiac deterioration and damage.
b. Prevent/minimize Na and water retention.
c. Eliminate or minimize symptoms of HF (increase quality of life).
d. Slow the progression of cardiac dysfunction.
e. Decrease mortality.
2. Management of fluid overload with diuretics
a. Short-term benefits (days)
i. Decreased jugular venous distension
ii. Decreased pulmonary congestion
iii. Decreased peripheral edema

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b. Intermediate-term benefits (weeks to months)

i. Decreased daily symptoms
ii. Improved cardiac function
iii. Increased exercise tolerance
c. Long-term benefits (months to years): no benefit on mortality
d. Diuretic caveats
i. Never use as the only therapy for HF because they have no effect on disease
progression or mortality
ii. If a patient has fluid overload, initiate and adjust therapy to result in 1 -2 lb of weight
loss per day (may be more aggressive in the inpatient setting).
iii. Chronic therapy should be adjusted to maintain a euvolemic state.
iv. Monitor and replace K and Mg as needed, especially with loop diuretics (goal with
cardiovascular disease is K of 4.0 mEq/L or higher and Mg of 2.0 mEq/L or higher to
minimize arrhythmias).
v. Loop diuretics are recommended because of greater diuretic capabilities,
a. Loop diuretics retain efficacy with decreased renal function.
vi. May combine loop diuretic with another class (e.g., thiazide diuretic) for synergy if
needed

Table 3.
Increase in Sodium
Diuretic Class Examples
Excretion (%)
Loop Furosemide, bumetanide, torsemide 25-30
Thiazide Hydrochlorothiazide, metolazone, 5-8
chlorthalidone
Potassium sparing Amiloride, triamterene, spironolactone 2-3

3. Neurohormonal blockade
a. Angiotensin-converting enzyme (ACE) inhibitors
i. Benefits of ACE inhibitor
(A) Decreased mortality (about 25% relative risk reduction vs. placebo)
(B) Decreased hospitalizations (about 30% relative risk reduction vs. placebo)
(C) Symptom improvement
(D) Improved clinical status
(E) Improved sense of well-being
ii. Mechanism of action
(A) Blocks production of angiotensin II
(1) Decreases sympathetic stimulation
(2) Decreases production of aldosterone and vasopressin
(3) Decreases vasoconstriction (afterload)
(B) Increases bradykinins (decreases their metabolism)
(1) Increases vasodilatory prostaglandins
iii. Place in therapy
(A) Should be used in all patients with LV dysfunction (even if asymptomatic)
iv. Dosing considerations
(A) Start low and increase dose every 1—4 weeks to goal.
(B) Benefits of high versus low doses

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(C) Patient may notice improvement in several weeks.

Table 4.
Drug Starting Dosage Target Dosage Maximal Dosage
Captopril 6.25 mg TID 50 mg TID 50 mg TID
Enalapril 2.5 mg BID 10 mg BID 20 mg BID
Lisinopril 2.5-5 mg/day 20 mg/day 40 mg/day
Perindopril 2 mg/day 8 mg/day 16 mg/day
Ramipril 1.25-2.5 mg/day 5 mg BID 10 mg/day
Trandolapril 1 mg/day 4 mg/day 4 mg/day

Note: Fosinopril and quinapril may be used; however, they do not have the same
magnitude of mortality-reducing data as the above-listed ACE inhibitor.
BID = 2 times/day; TID = 3 times/day.

v. Monitoring
(A) Serum creatinine, BP, and K in 1-2 weeks after starting or increasing the dose,
especially in high-risk individuals (e.g., those with systolic BP less than 90 mm
Hg, with serum Na concentrations less than 130 mmol/L, or receiving high loses
of loop diuretics)
(1) Serum creatinine may rise (up to a 0.5-mg/dL increase is acceptable) because
of renal efferent artery dilation (results in a slightly decreased glomerular
filtration rate).
(a) Rarely, acute renal failure occurs, especially if the patient is
intravascularly depleted (be careful to avoid overdiuresis).
(b) Use cautiously in patients with a baseline SCr more than 3.0 mg/dL
(NOT a contraindication; they should still be used, just with smaller
dosage changes and increased monitoring).
(2) Monitor BP and symptoms of hypotension (e.g., dizzy, light-headed).
(a) Blood pressure may be low to begin with because of low cardiac output.
BP = CO x SVR
(CO = cardiac output, SVR = systemic vascular resistance).
(b) In HF, as cardiac output increases because of decreased systemic vascular
resistance, BP may decrease slightly or remain about the same.
(c) Symptoms of hypotension are often not present with small dose
increases. Remember to treat the patient, not the number.
(3) Potassium may rise because of decreased glomerular filtration rate and
decreased aldosterone.
(a) Use cautiously in those with a baseline K greater than 5.0 mEq/L.
(B) Ninety percent of people tolerate ACE inhibitors.
(1) Angioedema (less than 1%) - could switch to angiotensin II receptor
blockers (ARBs; cross-reactivity is 2.5%)
(2) Cough (5%—10%) - could switch to ARBs (less than 1%)
b. ß -Blockers
i. Benefits of ß-blockade (when added to an ACE inhibitor)
(A) Decreased mortality (about 35% relative risk reduction vs. placebo)
(B) Decreased hospitalizations (about 25% relative risk reduction vs. placebo)
(C) Symptom improvement
(D) Improved clinical status

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(E) Improved sense of well-being

ii. Mechanism of action
(A) Blocks the effect of norepinephrine and other sympathetic neurotransmitters on
the heart and vascular system
(1) Decreases ventricular arrhythmias (sudden death)
(2) Decreases cardiac hypertrophy and cardiac cell death
(3) Decreases vasoconstriction and HR
(B) Carvedilol also provides ß-blockade.
(1) Further decreases systemic vascular resistance (afterload)
iii. Place in therapy
(A) Should be used in all stable patients (e.g., those not receiving intravenous inotropic
or diuretic therapy, those without peripheral and pulmonary congestion) with LV
dysfunction (even if asymptomatic)
iv. Dosing considerations
(A) Added to existing ACE inhibitor therapy (at least at a low dose) when HF
symptoms are stable and patients are euvolemic
(B) Start low and increase (double) the dose every 2-4 weeks (or slowly, if needed)
to goal.
(C) Avoid abrupt discontinuation; can precipitate clinical deterioration
(D) Patient may notice improvement in several months.
(E) Benefits of high versus low doses

Table 5.
Agent Starting Dosage Target Dosage
Bisoprolol 1.25 mg/day 10 mg/day
Carvedilol 3.125 mg BID a
25 mg BID
Metoprolol succinate 12.5-25 mg/day 200 mg/day
b
extended release
(metoprolol CR/XI.)
a
Fifty milligrams 2 times/day if weight is more than 85 kg.
b
Few or no data exist with metoprolol tartarate.
BID = 2 times/day; CR = controlled release; XL = extended release.

v. Monitoring
(A) Blood pressure, HR, and hypotension, dizziness (monitor in 1-2 weeks)
(1) Significant hypotension, bradycardia, or dizziness occurs in about 1% of
patients on ß-blocker therapy when titrated slowly. If these appear, lower the
dose by 50%. Discontinue the drug only if patient has heart block or is in
cardiogenic shock.
(2) With carvedilol, dizziness and hypotension are more common, usually
occurring within 24-48 hours of a dosage increase.
(3) The net decrease in HR at goal doses of ß-blocker is only 10-15 beats/minute
from baseline.
(B) Increased edema/fluid retention (monitor in 1-2 weeks)
(1) From 1% to 2% more common than placebo (in euvolemic, stable patients)
(2) Responds to diuretic increase
(C) Fatigue or weakness
(1) From 1% to 2% more common than placebo

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(2) Usually resolves spontaneously in several weeks

(3) May require dosage decrease or discontinuation
c. Aldosterone blockade
i. Patient population
(A) Class III and IV HF
(B) Left ventricular dysfunction immediately after MI
ii. Benefits of spironolactone in class III and IV HF
(A) Decreased mortality (30% relative risk reduction vs. placebo)
(B) Decreased hospitalizations for HF (35% relative risk reduction vs. placebo)
(C) Improved symptoms
iii. Benefits of eplerenone (a selective aldosterone blocker) with LV dysfunction after MI
(A) Decreased mortality (13% relative risk reduction vs. placebo)
iv. Mechanism of action
(A) Blocks effects of aldosterone in the kidneys, heart, and vasculature
(1) Decreases K and Mg loss
(a) Decreases ventricular arrhythmias
(2) Decreases Na retention
(a) Decreases fluid retention
(3) Eliminates catecholamine potentiation
(a) Decreases BP
(4) Blocks direct fibrotic actions on the myocardium
v. Place in therapy
(A) Should be considered in all patients with class III and IV HF who are receiving
background therapy with an ACE inhibitor, diuretic, and ß-blocker or after an MI
with LV dysfunction
(B) Avoid use in combination with both ACE inhibitor and ARB; the effects of all
three agents on K have not been adequately characterized.
vi. Dosing considerations
(A) Dosing
(1) Spironolactone 12.5—25 mg/day
(2) Eplerenone 25-50 mg/day
(B) Avoid use if SCr is greater than 2.5 mg/dL or serum K is greater than 5.0 mEq/L.
vii. Monitoring
(A) Potassium within 1 week of starting therapy
(1) Hyperkalemia was reported in only 2% of patients in the trial; however, in
practice, it occurs in about 10% of patients.
(2) Decrease dose by 50% or discontinue if K is greater than 5.5 mEq/L.
(B) Gynecomastia
(1) For spironolactone, gynecomastia was reported at a rate of 10% in clinical
trials.
(2) Eplerenone: A selective aldosterone blocker, it has only been studied in a
very narrow subset of the HF population (post-MI with decreased EF); may
be considered in class III and IV patients with painful gynecomastia
4. Digoxin
a. Benefits of digoxin
i. Improves symptoms
ii. Improves exercise tolerance

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iii. Small decrease in hospitalizations

iv. No effect on mortality
b. Mechanism of action (in HF) by Na-K adenosine triphosphatase inhibition
i. Decreases central sympathetic outflow by sensitizing cardiac baroreceptors
ii. Decreases renal reabsorption of Na
iii. Minimal increase in cardiac contractility because of the inhibition of Na-K adenosine
triphosphatase. This is not thought to cause beneficial effects in HF.
c. Place in therapy
i. Should be considered in patients with symptomatic LV dysfunction despite optimal
ACE inhibitor (or ARB), ß-blocker, spironolactone (if appropriate), and diuretic
therapy
d. Dosing considerations and monitoring
i. Serum concentrations of 0.5-0.8 ng/dL are effective in HF.
(A) Minimizes the risk of adverse effects and ventricular arrhythmias associated with
increased concentrations
(B) Risk of toxicity increased with age and renal dysfunction
(C) Risk of toxicity increased in the presence of hypokalemia or hypomagnesemia
ii. For most patients, 0.125 mg/day is adequate to achieve the desired serum
concentration. Loading doses are not recommended in the population.
iii. Useful initial agent for patient with concomitant AF
iv. Drug interactions. Digoxin concentrations are increased with concomitant:
(A) Clarithromycin-erythromycin
(B) Amiodarone, dronedarone
(C) Itraconazole, posaconazole, voriconazole
(D) Cyclosporine
(E) Verapamil
5. Hydralazine-isosorbide dinitrate
a. Benefits
i. Decreases mortality 39% versus placebo
ii. Decreases hospitalizations 33% versus placebo
a. Mechanism of action
i. Hydralazine
(A) Vasodilator
(B) Enhances effect of nitrates
ii. Isosorbide dinitrate
(A) Stimulates nitric acid signaling in the endothelium
c. Place in therapy
i. African Americans with NYHA class II—IV HF, already receiving an ACE inhibitor
(or ARB), ß-blocker, and diuretic therapy
ii. Decreases mortality versus placebo; however, ACE inhibitors have shown a 28%
relative risk reduction in death compared with hydralazine-isosorbide dinitrate.
iii. A reasonable alternative in patients unable to take an ACE inhibitor or ARB because
of severe renal insufficiency, hyperkalemia, or angioedema
d. Dosing consideration
i. Hydralazine (25-75 mg orally 3 or 4 times/day); isosorbide dinitrate (10-40 mg
orally 3 times/day). Titrate on the basis of BP.

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ii. Fixed-dose BiDil (hydralazine 37.5 mg plus isosorbide dinitrate 20 mg) with a goal
dose of 2 tablets 3 times/day
e. Monitoring
i. Headache
ii. Hypotension
iii. Drug-induced lupus with hydralazine
6. Angiotensin II receptor blockers
a. Have never been proved superior to ACE inhibitors at target HF dosages
b. Current role is as an ACE inhibitor substitute for patients unable to take an ACE inhibitor
because of cough.
c. The best ARB to use on the basis of available data is candesartan 32 mg/day or valsartan
160 mg 2 times/day (target doses).

Patient Case
3. Which one of J.T.'s (from case 2) drugs may be adversely affecting his cardiac prognosis?
A. Acetaminophen.
B. Sertraline.
C. Cilostazol.
D. Levothyroxine.

C. Nonpharmacologic Therapy
1. Prevent further cardiac injury.
a. Discontinue smoking.
b. Reduce weight if obese.
c. Control hypertension.
d. Control diabetes mellitus.
e. Minimize alcohol to two or fewer drinks per day for men, one or fewer drinks per day for
women
f. Eliminate alcohol if cardiomyopathy is alcohol induced.
2. Limit Na to 2 g/day.
3. Restrict fluid intake to 2 L/day if serum Na is less than 130 mmol/L or if there is fluid
retention despite aggressive diuresis and dietary Na restriction.
4. Modest exercise program
a. Benefits of therapy
i. Possible modest effects on all-cause hospitalization and all-cause mortality
ii. Safe for patients with HF
5. Annual influenza vaccine and pneumococcal vaccine every 5 years
6. Monitor and appropriately replace electrolytes (minimize risk of arrhythmias).
7. Monitor for thyroid disease.
a. Hypothyroidism may be masked by HF symptoms.
b. Hyperthyroidism will worsen systolic dysfunction.
8. Screen for and treat depression.

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D. Drugs to Avoid or Use with Caution

1. Nonsteroidal anti-inflammatory drugs (NSAIDs; including selective cyclooxygenase-2
inhibitors)
a. Promote Na and water retention
b. Blunt diuretic response
2. Corticosteroids
a. Promote Na and water retention
3. Class I and III antiarrhythmic agents ( except amiodarone and dofetilide)
a. Negative inotropic activity
b. Proarrhythmic effects
c. Amiodarone and dofetilide have been proven safe in patients with HF.
d. Avoid with dronedarone.
4. Calcium channel blocking agents ( except amlodipine and felodipine)
a. Negative inotropic activity
b. Neurohormonal activation
c. Amlodipine and felodipine have been proven safe in patients with HF.
5. Minoxidil
a. Fluid retention
b. Stimulation of the renin-angiotensin-aldosterone system
6. Thiazolidinediones
a. Fluid retention
7. Metformin
a. Increased risk of lactic acidosis (black box warning)
8. Anagrelide
a. Positive inotropic activity
b. Tachycardia
9. Amphetamines
a. α- and ß-agonist activity, tachycardia
b. Atrial and ventricular arrhythmias
10. Cilostazol
a. Inhibition of phosphodiesterase III, causing increased ventricular arrhythmias
11. Itraconazole
a. Negative inotropic activity
12. Pregabalin
a. Lower extremity edema, HF exacerbation
b. Inhibition of calcium channels

In contrast to the large number of trials and the patients with systolic dysfunction who have been studied,
there is a lack of objective data to guide therapy for patients with diastolic dysfunction. The following
recommendations are based primarily on the consensus opinion of cardiovascular experts.

E. General Treatment Goals of Diastolic Dysfunction

1. Control hypertension according to published guidelines.
a. Hypertension impairs myocardial relaxation.
b. Hypertension promotes cardiac hypertrophy.
2. Control tachycardia.
a. Tachycardia decreases the time for the ventricular and coronary arteries to fill with blood.
b. Control of HR improves symptoms of HF.

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c. Can use ß-blockers, dihydropyridine calcium channel blockers, and/or digoxin

3. Reduce preload (but not too much!).
a. Ventricular filling pressure is primarily determined by central blood volume.
b. Symptoms of breathlessness can be relieved by the use of diuretics or nitrates.
c. Patients with diastolic dysfunction are more preload-dependent for ventricular filling.
Decreasing the preload too much may cause unexpected hypotension.
4. Aggressively investigate, repair, and treat myocardial ischemia.
a. Myocardial ischemia impairs ventricular relaxation.
b. Any ischemia possibly contributing to diastolic dysfunction warrants aggressive therapy.

F. Pharmacologic Therapy for Diastolic Dysfunction

1. Angiotensin-converting enzyme inhibitors
a. Benefits of therapy
i. Reduction in unplanned hospitalizations
ii. Improvement in NYHA class
iii. Improvement in exercise tolerance
2. Angiotensin II receptor blockers
a. Benefits of therapy
i. The addition does not improve outcomes in patients with maximized background
therapy and well-controlled BP.
3. Digoxin
a. Benefits of therapy
i. No effect on all-cause mortality or on all-cause or cardiovascular hospitalizations
ii. Possible increase in unstable angina admissions
4. ß-Blockers, verapamil, diltiazem
a. Benefits of therapy
i. Targeted symptom relief

II. ATRIAL FIBRILLATION

Patient Case
4. P.M. is a 52-year-old man with a history of hypertension and a transient ischemic attack 2 years ago. He vis -
its his primary care doctor with the chief complaint of several weeks of a "fluttering" feeling in his chest on
occasion. He thinks it is nothing; however, his wife insists he have it checked. For his hypertension, he takes
verapamil 240 mg/day and aspirin 81 mg/day. His laboratory data from his past visit were all within normal
limits. His vital signs today include BP 130/78 mm Hg and HR 76 beats/minute. An electrocardiogram reveals
an irregularly irregular rhythm, with no p-waves, and a ventricular rate of 74 beats/minute. A diagnosis of
AF is made. Which one of the following is the best approach for managing his AF?
A. Begin digoxin 0.25 mg/day.
B. Begin atenolol 50 mg/day.
C. Begin amiodarone 400 mg 2 times/day, tapering to goal dose of 200 mg/day for the next 6 weeks.
D. Begin warfarin 7.5 mg/day; adjust to a goal INR of 2.5.

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A. Background
1. Prevalence
a . Most common arrhythmia: 2.2 million Americans
b . Prevalence increases with age.
c . Common comorbidity in patient with valvular heart disease or HF
2. Symptoms
a . Some patients have no symptoms.
b . At worst, an embolic event or symptoms of HF may be present.
c . Most patients have some degree of:
i. Palpitations
ii. Chest pain
iii. Dyspnea
iv. Fatigue
v. Light-headedness
vi. Syncope
d . Symptoms vary with ventricular rate, underlying functional status, AF duration, and
individual patient perceptions.
3. Classification (more than one of these may exist in a given patient):
a . Paroxysmal—spontaneous self-termination within 7 days of onset
b . Persistent—lasting more than 7 days
c . Permanent—a commonly used but arbitrary classification
d . Recurrent—two or more episodes

B. Pathophysiology
1. Cardiac conduction

Figure 2.

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2. Electrocardiogram findings
a. No p-waves
b. Irregularly, irregular rhythm
c. Rate may be fast or slow (depending on the rate of atrioventricular node conduction).

Figure 3.

3. Why do these abnormal impulses develop?

Table 6. Atrial Distension High Adrenergic Tone

Chronic hypertension Alcohol withdrawal
Mitral valve disease Thyrotoxicosis
Cardiomyopathy Sepsis
Congenital defects Binge drinking
Pulmonary hypertension Cocaine
Acute pulmonary embolus Amphetamines
Excessive theophylline, caffeine
Sympathomimetics
Surgery

C. Pharmacologic Therapy
1. Ventricular rate control
a. If patients have a rapid ventricular rate, atrioventricular node blockade is required.
b. The goal HR is 60-80 beats/minute at rest and 90-115 beats/minute during exercise.
c. Select the best agent based on individual clinical response and concomitant disease states
that may increase or decrease the desirability of one of the three approaches.
d. These therapies have no effect on cardioversion:
i. ß -Blockade
(A) Any agent with ß-blockade can be used and dosed to the goal HR.
(B) Selective ß 1 -antagonists, such as atenolol, may be preferred.
(C) Labetalol or carvedilol if additional ß-blockade is desirable (e.g., hypertension or
cocaine exposure).
(D) Sotalol or propafenone (class III antiarrhythmic) if rhythm control necessary
(E) Effective for controlling exercise-associated HR increases
ii. Calcium channel blockade
(A) Verapamil or diltiazem
(1) Avoid use if there is concomitant systolic dysfunction.
(2) May be preferred over ß-blocker in patients with asthma/severe chronic
obstructive pulmonary disease
(3) Also effective for controlling exercise-associated HR increases
iii. Digoxin

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(A) Often ineffective alone for controlling ventricular rate in AF, especially during
exercise or movement (because of minimal effectiveness with sympathetic
stimulation)
(B) Should be included in regimen if patient has systolic HF
(C) May also be effective if additional HR control is needed when a patient is
receiving a ß-blocker, diltiazem, or verapamil
2. Anticoagulation
3. The average annual stroke rate is 5% per year without anticoagulation.
a. A patient's individual risk may vary from about 1% to 20% per year based on his or her
risk factors. (This risk is INDEPENDENT of current cardiac status [i.e., normal sinus
rhythm or AF].)
b. Risk stratification and treatment determination

Table 7.

Adapted with permission from Lippincott, Williams & Wilkins. Fuster V, Ryden LE, Cannom DS,
et al.; American College of Cardiology/American Heart Association Task Force on Practice
Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart
Rhythm Association; Heart Rhythm Society. ACC/AHA/ESC 2006 guidelines for the management
of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and the European Society of Cardiology
Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the
Management of Patients with Atrial Fibrillation): developed in collaboration with the European
Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114:e257-e354.

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Table 8.

Adapted from Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ.
Validation of clinical classification schemes for predi cting stroke: results from the National
Registry of Atrial Fibrillation. JAMA 2001;285:2864-70.
Reprinted with permission from the American Medical Association.

e. Role of clopidogrel
i. ACTIVE A (New Engl J Med 2009;360:2066-78): Compared with aspirin alone,
patients with AF receiving 75 mg/day of clopidogrel and aspirin who had an
increased risk of stroke and for whom warfarin was unsuitable had a significant
reduction in major vascular events but an increased risk of bleeding.
ii. ACTIVE W (Lancet 2006:367:1903-12): Compared with clopidogrel and aspirin,
warfarin had a significantly lower rate of vascular events in patients with AF plus one
or more risk factors for stroke. No difference existed in bleeding between groups.
f. Bleeding
i. Minor hemorrhage increased with therapeutic warfarin therapy
ii. Major hemorrhage not increased with warfarin therapy with INR 2—3
iii. Risk of intracranial hemorrhage increased with INR greater than 4

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Patient Case
5. H.D. is a 67-year-old man with a history of hypertension, moderate mitral valve insufficiency, and AF for 4
years. His drugs include ramipril 5 mg 2 times/week, sotalol 120 mg 2 times/week, digoxin 0.125 mg/day,
and warfarin 5 mg/day. He visits his primary care physician today with increased fatigue on exertion and
palpitations with no lower or upper extremity edema. His vital signs today include BP 115/70 mm Hg and
HR 88 beats/minute; all laboratory results are within normal limits, except for an INR of 2.8. His electro -
cardiogram shows AF. An echocardiogram shows an LVEF of 35%-40%. Which one of the following is the
best approach for managing his AF?
A. Discontinue sotalol and begin metoprolol succinate 12.5 mg/day.
B. Add aspirin 325 mg/day.
C. Discontinue sotalol and begin amiodarone 400 mg 2 times/day, tapering to goal dose of 200 mg/day for
the next 6 weeks.
D. Add metoprolol 25 mg 2 times/day.

4. Rhythm control: Since the publication of the Atrial Fibrillation Follow-up Investigation of
Rhythm Management (AFFIRM) trial (N Engl J Med 2002;34:1825-33), it has been known
that maintaining normal sinus rhythm offers no advantage over controlling the ventricular rate
(in the typical elderly patient with AF). In fact, the rhythm control group had a higher incidence
of hospitalizations, gastrointestinal adverse effects, and symptoms of HF. However, in specific
patients with intractable and intolerable symptoms, despite adequate rate control (dyspnea and
palpitations), restoration and maintenance of normal sinus rhythm may be desirable.

Table 9.
Pros Cons
Rate control Easy to achieve and maintain Electrical and structural remodeling
strategy because of continued atrial fibrillation
makes future attainment of NSR virtually
impossible
Rhythm control If patient is symptomatic with fatigue Adverse effects of medications, cost of
strategy and exercise intolerance, these may medications and monitoring, likelihood
improve if NSR is attained (especially of atrial fibrillation recurrence
in the patient with HF)
HF = heart failure; NSR = normal sinus rhythm.

a. If cardioversion is attempted (electric or pharmacologic), the absence of atrial thrombi

must be ensured.
i. Thrombi present plus cardioversion = 91% stroke rate
ii. Without anticoagulation (caused by decreased or stagnant bloodflow in the atria)
(A) Atrial fibrillation for greater than 48 hours = 15% rate of atrial thrombus
(B) Atrial fibrillation for greater than 72 hours = 30% rate of atrial thrombus
b. Ensure safe cardioversion by either:
i. Transesophageal echocardiogram to visualize the atria OR
ii. Three or more weeks of therapeutic anticoagulation (INR greater than 2.0)
c. Oral pharmacologic agents to induce/maintain normal sinus rhythm
i. Class I antiarrhythmics: contraindicated in patients with FIF
(A) Often third line because of frequent dosing requirements and adverse effect
profiles; some patients require hospitalization for initiation because of
proarrhythmic effects; only about 50% efficacy at 1 year

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(1) Quinidine
(2) Disopyramide
(3) Propafenone
(4) Flecainide
(B) However, flecainide and propafenone may be considered first-line therapies for
patients without structural heart disease (see figure below).
ii. Class III antiarrhythmics
(A) Amiodarone: 85%-95% efficacy
(1) In addition, has electrophysiologic properties of classes I-IV
(2) Oral loading dose required (400 mg/day 2 or 3 times/day x 2 weeks and
then 400 mg/day for 4 weeks, followed by a 200-mg/day maintenance dose).
Achieving a loading dose of 10 g is desirable. Many different regimens exist.
(3) Long half-life of about 60 days
(4) In addition, has atrioventricular nodal blocking properties; may help control
HR if AF recurs
(5) Hepatically metabolized inhibitor of cytochrome P450 (CYP) enzymes
CYP3A4, CYP1A2, CYP2C9, CYP2D6, and P-glycoprotein
(6) Minimal incidence of ventricular arrhythmias
(7) Drug interactions (many)
(a) Digoxin - Increased digoxin exposure. Lower initial digoxin dose by 50%
(b) Warfarin - Increased warfarin exposure. Lower warfarin dose by 25%
(c) Simvastatin — Increased simvastatin exposure. Do not exceed dose of 20
mg/day.
(d) ß-Blockers (particularly carvedilol) -Additive bradycardia, increased
ß-blocker exposure
(8) Extensive monitoring for noncardiac adverse effects
(a) Liver function tests: baseline and every 6 months
(b) Thyroid function tests: baseline and every 6 months
(c) Chest radiography: baseline and annually
(d) Pulmonary function tests (including D L CO 2 [carbon dioxide diffusion in
the lungs]): baseline and for unexplained dyspnea or chest radiographic
abnormalities
(e) Ophthalmologic examination: for symptoms of visual impairment
iii. Class I-IV agents
(A) Dronedarone: 21%—25% efficacy
(1) Amiodarone analog that specifically lacks the iodine moiety that contributes
to the pulmonary, thyroid, hepatic, and ocular toxicity of amiodarone
(2) Has complex antiarrhythmic properties that span all classes of the Vaughan -
Williams classification
(3) Dose: 400 mg twice daily with morning and evening meal
(4) Hepatically metabolized CYP3A4 substrate and a moderate CYP3A4,
CYP2D6, and P-glycoprotein inhibitor
(5) Half-life only 24 hours
(6) Can increase SCr within 7 days (by 0.1 mg/dL - not clinically important)
(7) Contraindicated in NYHA class II or III HF with recent decompensation
requiring hospitalization, severe liver impairment, NYHA class IV HF, HR
less than 50 beats/minute, and strong CYP3A4 inhibitors

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(8) Compared with placebo in the ATHENA trial (N Engl J Med 2009;360:668-
78), high-risk patients with a history of paroxysmal or persistent AF or atrial
flutter within the past 6 months receiving dronedarone had a lower incidence
of hospitalization for cardiovascular causes or death from any cause; risk of
cardiovascular death, death from arrhythmias, and incidence of stroke.
(9) Based on Andromeda study (N Engl J Med 2008;358:2678-87), dronedarone
compared with placebo showed an increased mortality in patients with HF
(LVEF less than 35% and NYHA classes II-IV).
(10) One meta-analysis (JAm Coll Cardiol 2009;54:1089-95) found dronedarone
less effective than amiodarone for the maintenance of sinus rhythm, but with
fewer adverse effects.
(11) Drug interactions
(a) Digoxin: increased digoxin exposure, so lower dose of digoxin by 50%
(b) Diltiazem, verapamil, ß-blockers: excessive bradycardia and increased
exposure of these agents, so initiate these drugs at lowest dose.
Diltiazem and verapamil can increase dronedarone exposure, so monitor
electrocardiogram.
(c) Statins with CYP3A metabolism: Increased statin exposure. Follow statin
package labeling for CYP3A4 inhibitors.
(d) CYP3A4 inhibitors: AVOID
(e) Cyclosporine, tacrolimus, sirolimus: Increased exposure of these agents,
monitor serum concentrations closely
(12) U.S. Food and Drug Administration Risk Evaluation and Mitigation Strategy
(a) See the following Web site: www.fda.gov/downloads/Drngs/DriigSafety/
PostmarketDrugSafetylnformationforPatientsandProviders/
UCM187494.pdf
a. Sotalol: 50%-60% efficacy
1. Renal excretion; hence, dose adjustment and vigilant QTc (corrected
noninvasive cardiac output) monitoring necessary in renal impairment
2. May be initiated in outpatient setting in patients with little or no heart
disease, normal baseline QTc, normal serum electrolytes, and normal renal
function
3. Contraindicated in patients with HF and CrCl less than 40 mL/minute
b. Dofetilide: 50% - 60% efficacy
1. Must be initiated in the hospital (2- to 3-day stay). Dose titrated on the basis
of renal function and QTc response
2. Hepatically metabolized by CYP3A
3. Renal elimination through renal cationic secretion; check QTc if renal
function acutely declines
4. Safe to use in patients with HF
5. Drug interactions:
a. Cimetidine, verapamil, ketoconazole, hydrochlorothiazide, and
trimethoprim alone or in combination with sulfamethoxazole: AVOID
b. CYP3A4 inhibitors: increased dofetilide exposure, so use with caution
c. Triamterene, metformin, amiloride: increased dofetilide exposure, so use
with caution

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iii. The choice of agent may depend on comorbidities.

Figure 4.
CAD = coronary artery disease; LVH = left ventricular hypertrophy.
Adapted with permission from Lippincott, Williams & Wilkins. Fuster V, Ryden LE, Cannom
DS, et al.; American College of Cardiology/American Heart Association Task Force on Practice
Guidelines; European Society of Cardiology Committee for Practice Guidelines; European Heart
Rhythm Association; Heart Rhythm Society. ACC/AHA/ESC 2006 guidelines for the management
of patients with atrial fibrillation: a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines and the European Society of Cardiology
Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the
Management of Patients with Atrial Fibrillation): developed in collaboration with the European
Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114:e257-e354.

5. Nonpharmacologic therapies
a. Electrical cardioversion (low-energy cardioversion, sedation highly desirable, can be used
in an emergency if patient is hemodynamically unstable)
b. Atrioventricular nodal ablation: Ablate atrioventricular node and chronically pace the
ventricles.
c. Pulmonary vein ablation: This relatively new therapy ablates the origin of the abnormal
atrial foci, which is often near the pulmonary vein-atrial tissue intersection.

III. HYPERTENSION

Definition: Hypertension is considered a BP of 140/90 mm Hg or higher or antihypertensive drug therapy.

A. Background
1. Statistics
a. Most common chronic disease in the United States
b. Affects 50 million Americans

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c. Normotensive 50-year-old lifetime risk of developing hypertension is 90%.

d. For each 20-mm increase in systolic BP and 10-mm increase in diastolic BP, there is a
2-fold increased risk of cardiovascular disease (e.g., stroke, MI).
e. Only 31% of patients with hypertension have it under adequate controls
2. Etiology
a. Essential hypertension: 90% (no identifiable cause)
i. Contributed to by obesity and Na intake
b. Secondary hypertension
i. Primary aldosteronism
ii. Renal parenchymal disease
iii. Thyroid or parathyroid disease
iv. Medications (e.g., cyclosporine, NSAIDs, sympathomimetics)
3. Diagnosis
a. Periodic screening for all individuals older than 21 years
b. Patient seated quietly in chair for at least 5 minutes
c. Use appropriate cuff size (bladder length at least 80% the circumference of the arm).
d. Take BP at least 2 times, separated by at least 2 minutes.
e. The average BP on two separate visits is required to diagnose hypertension accurately.
4. Benefits of lowering BP
a. Forty percent decrease in stroke
b. Twenty-five percent decrease in MI
c. Fifty percent decrease in HF.
5. Effects of lifestyle modifications on BP

Table 10.
Modification Recommendation Approximate Systolic
BP Reduction
Weight reduction Attain/maintain BMI less than 25 kg/m 2 5-20 mm Hg per 10-kg
(if more than 25 kg/m 2 ) weight loss
Adopt DASH eating plan (includes Consume a diet rich in fruits, vegetables, 8-14 mm Hg
substantial potassium intake) and low-fat dairy products with a reduced
content of saturated and total fat
Dietary sodium restriction Reduce dietary sodium intake to no more 2-8 mm Hg
than 2.4 g of sodium
Physical activity Engage in regular aerobic physical activity 4-9 mm Hg
such as brisk walking (at least 30 minutes/
day, most days of the week)
Moderation of alcohol Limit consumption to: 2-4 mm Hg
consumption Men: 2 drinks/day
Women: 1 drink/day

BMI = body mass index; BP = blood pressure; DASH = Dietary Approaches to Stop Hypertension.

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Patient Cases
6 D.W. is a 50-year-old African American man being discharged from the hospital after an acute MI. His
medical history is significant for hypertension. He was taking hydrochlorothiazide 25 mg/day before hospi-
talization. An echocardiogram before discharge shows an LVEF of more than 60%. His vital signs include
BP 150/94 mm Hg and HR 80 beats/minute. Which one of the following is the best approach for managing
his hypertension?
A. Discontinue hydrochlorothiazide and add diltiazem.
B. Continue hydrochlorothiazide and add metoprolol.
C. Discontinue hydrochlorothiazide and add losartan.
D. Continue hydrochlorothiazide and add losartan.

7. T.J. is a 45-year-old white woman with a history of type 2 diabetes mellitus treated with glyburide 5 mg/
day. She presents to the clinic for a routine follow-up of her diabetes. Her BP today (average of two readings)
is 138/88 mm Hg, HR is 70 beats/minute, and laboratory results are Na 140 mEq/L, K 4.0 mEq/L, CI 102
mEq/L, bicarbonate 28 mEq/L, BUN 14 mg/dL, and SCr 1.8 mg/dL. Of note, at her last visit, her BP was
136/85 mm Hg. Which one of the following is best for managing her hypertension at this time?
A. Begin lifestyle modifications.
B. Begin lifestyle modifications and add losartan 50 mg/day.
C. Begin lifestyle modifications and add lisinopril 2.5 mg/day.
D. Begin lifestyle modifications and add atenolol 25 mg/day.

B. Therapeutic Management
1. Patient classification and management in adults
a. Primary classification based on systolic BP

Table 11.
BP Classification Systolic BP Diastolic BP Lifestyle
(mm Hg) (mm Hg) Modification
Normal < 120 AND < 80 Encourage
Prehypertension 120-139 OR 80-89 Yes
Stage 1 140-159 OR 90-99 Yes
hypertension
Stage 2 □ 160 OR □ 100 Yes
hypertension

BP = blood pressure.

2. Select treatment goal.

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Table 12.

Disclaimer: The JNC7 (2003) recommends a goal BP of less than 140/90 mm Hg for all patients, except for
diabetes and chronic kidney disease, in which they recommend less than 130/80 mm Hg. Therefore, the
AHA 2007 guidelines are more recent, include more updated evidence, and are more aggressive. Follow the
AHA recommendations for now until the JNC8 guidelines are published (in 2010). The JNC8 will then be
the primary guidelines to follow.
Adapted with permission from Lippincott, Williams & Wilkins. Rosendorff C, Black HR, Cannon CP, et al.;
American College of Cardiology/American Heart Association Council for High Blood Pressure Research
and the Councils on Clinical Cardiology and Epidemiology and Prevention. Treatment of hypertension in
the prevention and management of ischemic heart disease. A scientific statement from the AHA Council for
High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention.
Circulation 2007;115:2761-88.

3. Select appropriate therapy.

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Figure 5.

NOTE: Strength of recommendation [A, B, and C = good, moderate, and poor evidence to support recommendation]
and quality of evidence [1 = Evidence from more than 1 properly randomized, controlled trial. 2 = Evidence from at
least 1 well-designed clinical trial with randomization, from cohort or case-controlled analytic studies; or dramatic
results from uncontrolled experiments or subgroup analyses. 3 = Evidence from opinions of respected authorities,
based on clinical experience, descriptive studies, or reports of expert communities] are in brackets.

ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; CCB = calcium channel blocker.

Modified from Saseen JJ, MacLaughlin EJ. Hypertension. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR,
Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiological Approach, 7th ed. New York: McGraw-Hill,
2008:Chapter 15.

4. Considerations with specific antihypertensive agents

a. ß-Blockers
i. Caution with asthma, severe chronic obstructive pulmonary disease (especially higher
doses) because of pulmonary ß-blockade
ii. Increased risk of developing diabetes compared with ACE inhibitor, ARB, and
calcium channel blocker; use caution in patients at high risk of diabetes mellitus (e.g.,
family history, obese)
iii. May mask some signs of hypoglycemia in patients with diabetes mellitus
iv. May cause depression
b. Thiazides
i. May worsen gout by increasing serum uric acid
ii. Increased risk of developing diabetes compared with ACE inhibitor, ARBs, and
calcium channel blocker; use caution in patients at high risk of diabetes mellitus (e.g.,
family history, obese)
iii. May assist in the management of osteoporosis by preventing urine calcium loss
c. Angiotensin-converting enzyme inhibitors and ARBs
i. Contraindicated in pregnancy
ii. Contraindicated with bilateral renal artery stenosis
iii. Monitor K closely, especially if renal insufficiency exists or another K-sparing drug
is in use.
iv. Presence of diabetic nephropathy should influence choice of ACE inhibitor versus ARB

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Table 13.
Nephropathy Agent
Type 1 Any level of proteinuria ACEI
Type 2 Microalbuminuria ACEI or ARB
Type 2 Microalbuminuria and renal insufficiency (i.e., elevated ARB
serum creatinine)
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker.

4. Considerations within specific patient populations

a. Patients with ischemic heart disease: Potent vasodilators may cause reflex
tachycardia, thereby increasing myocardial oxygen demand (hydralazine, minoxidil,
and dihydropyridine calcium channel blocker) (can attenuate this by also using an
atrioventricular nodal depressant (non-dihydropyridine calcium channel blocker or
ß-blocker)
b. Elderly patients:
i. Caution with antihypertensive agents and orthostatic hypotension
ii. Initiate with low dose and titrate slowly.
c. African American patients: ß-Blockers and ACE inhibitors are generally less effective
as monotherapy than in white patients; however, combination therapy with thiazides
improves effectiveness and should still be used if comorbid conditions dictate.
d. Pregnant women
i. Methyldopa and hydralazine are recommended if a new therapy is initiated. Most
antihypertensives (except for ACE inhibitors and ARBs) can be safely continued in
pregnancy.
5. Monitoring
a. Have the patient return in 4 weeks to assess efficacy.
b. May have patient follow-up sooner if BP particularly worrisome
c. If there is an inadequate response from the first agent (and adherence verified) and no
compelling indication exists, initiate therapy with a drug from a different class.

IV. CHRONIC CAD AND CHRONIC STABLE ANGINA

Coronary artery disease is a general term that does not discriminate between the various
phases the individual may cycle between for several decades. These phases include
asymptomatic disease, stable angina, progressive angina, unstable angina, non -ST-segment
elevation MI, and ST-segment elevation MI.
Based on the manifestations a patient is experiencing, some therapies may be added or
modified. However, several basic treatment rules apply to all individuals with CAD,
regardless of the symptoms they may experience.

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The following mnemonic, developed for patients with chronic stable angina, can be applied to
all patients with CAD.
A = Aspirin and Antianginal Therapy
B = ß-Blocker and BP
C = Cigarette Smoking and Cholesterol
D = Diet and Diabetes
E = Education and Exercise
Obviously, not all patients with CAD have diabetes or smoke cigarettes, but it is a way to
remember the primary areas that should be addressed, as applicable, in all patients with CAD.
A few important recommendations:
Weight reduction/maintenance to 18.5-24.9 kg/m2;
Physical activity for 30-60 minutes/day 7 days/week (minimum of 5 days/week);
Low-density lipoprotein cholesterol less than 100 mg/dL;
Blood pressure less than 130/80 mm Hg;
No smoking and no environmental exposure to smoke;
Reduce intake of saturated fats (to less than 7% of total calories), trans-fatty acids, and
cholesterol (to less than 200 mg/day);
If diabetic, glycosylated hemoglobin less than 7%; and
Influenza vaccine each year

Patient Cases
8. L.J., a 58-year-old white man, is discharged from the hospital after a non-ST-segment elevation MI. His
medical history is significant for hypertension. He was taking hydrochlorothiazide 12.5 mg/day before
hospitalization. An echocardiogram shows an LVEF of more than 60%. His vital signs include BP 130/65
and HR 64 beats/minute, and he states that he feels great. His drug regimen consists of aspirin 81 mg/day,
atenolol 50 mg/day, hydrochlorothiazide 25 mg/day, atorvastatin 80 mg/day, and sublingual nitroglycerin 0.4
mg as needed for chest pain. Which of the following represents the best action to take in response to this
discharge regimen?
(1) Discontinue hydrochlorothiazide; add diltiazem extended release 240 mg/day.
(2) Continue hydrochlorothiazide; add amlodipine 5 mg/day.
(3) Discontinue hydrochlorothiazide; add ramipril 5 mg/day.
(4) Continue hydrochlorothiazide; add vitamin E.

9. L.W. is a 64-year-old woman with a significant coronary disease history, having had two Mis and three stent
placements in the past 10 years. Her LVEF is more than 60%. She has developed shortness of breath and
chest heaviness with activity for the past several months, despite being adherent to her medications. She
says she is requiring up to three doses of her sublingual nitroglycerin per day; however, she has severely
curtailed her activity to avoid the discomfort. She takes aspirin 325 mg/day, simvastatin 40 mg every night,
enalapril 10 mg 2 times/day, and metoprolol titrate 50 mg 2 times/day. Her BP is 132/80 mm Hg, and her
HR is 72 beats/minute. Which one of the following regimens is best to improve her stable angina symptoms
and increase her activity level?
a. Discontinue metoprolol tartrate and begin diltiazem extended release 240 mg/day.
b. Have her take a sublingual nitroglycerin before exertion.
c. Add isosorbide mononitrate 60 mg every morning.
d. Increase metoprolol tartrate to 100 mg 2 times/day and add isosorbide mononitrate 60 mg every
morning.

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 Outpatient Cardiology

A. Therapeutic Management
1. Antiplatelet therapy
a) Aspirin
a. Inhibits synthesis of thromboxane A 2 ,
b. Indicated in all patients with CAD, unless contraindicated
c. Dose at 75-162 mg/day.
d. Decreases cardiovascular events by about one-third
b)Clopidogrel
a. Prevents adenosine diphosphate-mediated platelet activation
b. A dose of 75 mg/day if aspirin absolutely contraindicated
c. Magnitude of benefit not clear; however, appears to be about that of aspirin
c) Dipyridamole: should be avoided in symptomatic CAD
a. Increases exercise-induced myocardial ischemia
b. No benefit over aspirin in the absence of symptomatic CAD
2. Lipid-lowering therapy (see Ambulatory Care—Disorders of Lipid Metabolism)
a. Low-density lipoprotein cholesterol should be less than 100 mg/dL.
b. Reduction in LDL-C to less than 70 mg/dL or use of a high-dose statin is reasonable.
c. In high- or moderately high-risk patients, the intensity of lipid-lowering therapy should
be sufficient to achieve a 30% - 40% reduction in LDL-C.
d. If triglycerides are 200-499 mg/dL, non-high-density lipoprotein concentrations should
be less than 130 mg/dL; however, less than 100 mg/dL is also reasonable if triglycerides
are 200-499 mg/dL or higher.
e. Can consider the addition of plant stanols/sterols (2 g/day) or viscous fiber (greater than
10 g/day) to lower LDL-C
f. For risk reduction, encourage omega-3 fatty acids in the form of fish or capsule (1 g/day)
in all patients.
3. Angiotensin-converting enzyme inhibitors
a. Angiotensin-converting enzyme inhibitors (specifically ramipril 10 mg/day) have been
shown to greatly decrease cardiovascular events in patients with CAD (and no LV
dysfunction) at high risk of subsequent cardiovascular events.
b. An ACE inhibitor should be considered in patients with an LVEF of 40% or less and in
patients with hypertension and established CAD, diabetes mellitus, and/or chronic kidney
disease.
c. Consider using in lower-risk patients with a mildly reduced or normal LVEF in whom
cardiovascular risk factors are well controlled and revascularization has been performed.
d. Postulated mechanisms: plaque stabilization
4. Angiotensin II receptor blockers
a. Recommended for those with hypertension, those with indications for and intolerance of
ACE inhibitors, those with HF, or those who have had an MI with an EF of 40% or less

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 Outpatient Cardiology

Additional Therapies for Chronic Stable Angina

Definition: predictable angina symptoms with exertion

Goal: Reduce symptoms of ischemia, increase physical function, and improve quality of life.
In general, achieved by either:
Decreasing myocardial oxygen demand OR
Increasing myocardial oxygen supply
5. ß -Blockers
a. Pharmacologic effects: decreased inotropy and HR (decreased oxygen demand)
b. Goal resting HR 55-60 beats/minute (less than 50 beats/minute if angina symptoms
continue)
c. Goal exercise HR of no more than 75% HR associated with angina symptoms
d. Contraindications: severe bradycardia (HR less than 50 beats/minute), high-degree
atrioventricular block (without pacemaker), sick sinus syndrome (without pacemaker)
6. Calcium channel blockers
a. Pharmacologic effects
i. Decrease coronary vascular resistance and increase coronary bloodflow (increase
oxygen supply)
ii. Negative inotropy, to varying degrees; nifedipine much greater than amlodipine and
felodipine (decrease oxygen demand)
iii. Decrease HR (verapamil and diltiazem only)
b. Place in therapy
i. Added to ß-blocker therapy to achieve HR goals
ii. Instead of ß-blocker therapy when unacceptable adverse effects emerge
iii. Short-acting calcium antagonists (nifedipine, nisoldipine) have been associated
with increased cardiovascular events and should be avoided (except in slow -release
formulations).
c. Contraindications for non-dihydropyridines : systolic HF, severe bradycardia, high-
degree atrioventricular block (without pacemaker), and sick sinus syndrome (without
pacemaker)
d. Contraindications for dihydropyridines: LV dysfunction (except amlodipine and
felodipine)
7. Nitrates
a. Pharmacologic effects:
i. Endothelium-dependent vasodilation, dilates epicardial arteries and collateral vessels
(increased oxygen supply)
ii. Decreased LV volume because of decreased preload mediated by vasodilation
(decreased oxygen demand)
b. Place in therapy
i. A scheduled nitrate is useful in conjunction with ß-blockade or non-dihydropyridine
calcium channel blocker (which blunts the reflex sympathetic tone with nitrate
therapy).
ii. As-needed sublingual or spray nitrate is necessary to relieve effort or rest angina.
iii. In addition, as-needed nitrates can be used before exercise to avoid ischemic
episodes.

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 Outpatient Cardiology

c. Contraindications: hypertrophic obstructive cardiomyopathy, inferior wall MI, severe

aortic valve stenosis, sildenafil and vardenafil within 24 hours, tadalafil within 48 hours
8. Aldosterone receptor blockers
a. Place in therapy
i. Can be used in patients post-MI without significant renal dysfunction (SCr should be
less than 2.5 mg/dL for men and 2.0 mg/dL for women) or hyperkalemia (K should
be less than 5.0 mEq/L) who are receiving a ß-blocker and ACE inhibitor (or ARB),
have an EF of 40% or less, and have either HF or diabetes mellitus
9. Ranolazine
a. Pharmacologic effects
i. Inhibits myocardial fatty acid oxidation, causing increased glucose oxidation (a less
oxygen-consuming process)
ii. Increases "oxygen efficiency"
b. Place in therapy
i. Ideal role is not clear. Currently, either as monotherapy or as an add-on to maximally
tolerated conventional therapy (ß-blocker plus calcium channel blocker plus nitrate)
with continued symptoms
ii. Important points
(A) Heart rate or BP effects are not present; thus, bradycardia and hypotension are
not a concern.
(B) Dose-related QT prolongation
(C) Metabolized by CYP3A
(1) Avoid in hepatic dysfunction or disease.
(2) Avoid use with strong 3A inhibitors including ketoconazole, itraconazole,
clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir.
(3) Avoid use with 3A inducers such as rifampin, rifabutin, rifapentine,
phenobarbital, phenytoin, carbamazepine, and St. John's wort.
(4) Limit the dose to 500 mg 2 times/day in patients receiving including
diltiazem, verapamil, aprepitant, erythromycin, fluconazole, and grapefruit
juice.

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 Outpatient Cardiology
REFERENCES
Heart Failure
1. Hunt SA, Abraham WT, Chin MH, et al. 2009
focused update incorporated into the ACC/AHA
2005 guidelines for the diagnosis and management
of heart failure in adults. A report of the American
College of Cardiology Foundation/American Heart
Association Task Force on Practice Guidelines
developed in collaboration with the International
Society for Heart and Lung Transplantation. J Am
Coll Cardiol 2009;53:el-e90.
2. Jackevicius CA, Page RL, Chow S, et al. High im-
pact articles related to the management of heart fail-
ure: 2008 update. Pharmacotherapy 2009;29:82-
120.
3. Amabile CM, Spencer AP. Keep your heart failure
patient safe: a review of potentially dangerous med-
ications. Arch Intern Med 2004;164:709-20.
4. Adams KF, Lindenfeld J, Arnold JMO, et al. HFSA
2006 comprehensive heart failure practice guide-
line. J Card Fail 2006;12:el-el22.
Atrial Fibrillation
1. Fuster V, Ryden LE, Cannom DS, et al. ACC/
AHA/ESC 2006 guidelines for the management
of patients with atrial fibrillation: a report of the
American College of Cardiology/American Heart
Association Task Force on Practice Guidelines
and the European Society of Cardiology Commit-
tee for Practice Guidelines (Writing Committee to
Revise the 2001 Guidelines for the Management
of Patients with Atrial Fibrillation). Circulation
2006;114:e257-e354.
2. Singer DE, Albers GW, Dalen JE, et al. Antithrombot-
ic therapy in atrial fibrillation. Chest 2008;133:546S-
592S.
3. The Atrial Fibrillation Follow-up Investigation of
Rhythm Management (AFFIRM) Investigators.
A comparison of rate control and rhythm control
in patients with atrial fibrillation. N Engl J Med
2002;347:1825-33.
Hypertension
1. Chobanian AV, Bakris GL, Black HR, et al. The
Seventh Report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment
of High Blood Pressure: the JNC 7 report. JAMA
2003;289:2560-72.
2. Rosendorff C, Black HR, Cannon CP, et al. Treat-
ment of hypertension in the prevention and man-
© 2010 American College of Clinical Pharmacy
32
agement of ischemic heart disease: a scientific
statement from the American Heart Association
Council for High Blood Pressure Research and the
Councils on Clinical Cardiology and Epidemiology
and Prevention. Circulation 2007;115:2761-88.
3. Appel LJ, Brands MW, Daniels SR, et al. Dietary
approaches to prevent and treat hypertension: a sci-
entific statement from the American Heart Associa-
tion. Hypertension 2006;47:296-308.
CAD and Chronic Stable Angina
1. Gibbons RJ, Abrams J, Chatterjee K, et al. ACC/
AHA 2002 guideline update for the management
of chronic stable angina: a report of the American
College of Cardiology/American Heart Association
Task Force on Practice Guidelines (Committee to
Update the 1999 Guidelines for the Management of
Patients with Chronic Stable Angina). Circulation
2006:114:e257-e354.
2. Gibbons RJ, Abrams J, Chatterjee K, et al. 2007
chronic angina focused update of the ACC/AHA
2002 guidelines for the management of patients
with chronic stable angina. A report of the Ameri-
can College of Cardiology/American Heart Asso-
ciation Task Force on Practice Guidelines Writing
Group to develop the focused update of the 2002
guidelines for the management of patients with
chronic stable angina. Circulation 2007;116:2762-
72.
3. Smith SC, Allen J, Blair SN, et al. ACC/AHA
guidelines for the secondary prevention for patients
with coronary and other atherosclerotic vascular
disease: 2006 update. Circulation 2006;13:2363-72.
 Outpatient Cardiology
ANSWERS AND EXPLANATIONS TO PATIENT CASES
1. Answer: A
At this time, the best option is to increase L.S.'s
carvedilol to the goal dose of 25 mg 2 times/day. Despite
her HR of 68 beats/minute, it is safe to increase the
ß-blocker. Appropriate monitoring would include signs
and symptoms of hypotension and bradycardia. Her
ACE inhibitor is already at the target dose; hence, it
should be increased to the maximal dose only if there is
another indication to do so (hypertension or proteinuria).
Spironolactone 25 mg is the recommended dose for HF;
increasing to 50 mg/day is not warranted. Her digoxin
concentration of 0.7 ng/dL is within the desired range
of 0.6-1.0 ng/dL, so no dosage increase is warranted
because this would not improve efficacy and would only
increase the risk of toxicity/arrhythmia.
2. Answer: B
Increasing the ACE inhibitor to target doses should be
achieved in all patients, if possible. J.T.'s BP of 120/72
mm Hg safely permits increasing the enalapril from 5
mg to 10 mg 2 times/day. There is no consensus that
carvedilol is preferred over extended-release metoprolol
for patients with HF. Spironolactone is not appropriate
to initiate because J.T.'s HF is not NYHA class III or
IV, and his baseline SCr concentration is greater than 2.5
mg/dL. Digoxin should be added only in patients who
continue to have symptoms or hospitalizations despite
optimal therapy with an ACE inhibitor, ß-blocker, and
diuretic. J.T. has minimal symptoms, and his therapy has
opportunities for optimization.
3. Answer: C
Cilostazol, a phosphodiesterase III inhibitor, is associated
with an increased risk of ventricular arrhythmias and
death in patients with HF. Acetaminophen is the drug
of choice for mild to moderate pain in patients with
HF because NSAIDs can lead to water retention and
worsening HF symptoms. The selective serotonin
reuptake inhibitors have no contraindications to
use. Properly dosed thyroid replacement therapy,
as evidenced by his therapeutic thyroid-stimulating
hormone concentration, is also beneficial because both
hypothyroidism and hyperthyroidism have negative
consequences in patients with HF.
4. Answer: D
The patient is experiencing minimal symptoms with his
AF; thus, an antiarrhythmic should not be considered.
Even if he had significant symptoms with his AF, the
noncardiac adverse effects of amiodarone would make
it an unattractive antiarrhythmic in a healthy 52-year-
© 2010 American College of Clinical Pharmacy
33
old man. His ventricular rate is well controlled with his
verapamil therapy; hence, no additional atrioventricular
node blockade is warranted with either a ß-blocker or
digoxin. If additional atrioventricular node blockade
were desired, digoxin would not be ideal because of a
significant drug interaction with his verapamil therapy.
P.M. has a significant risk factor for stroke with AF and a
prior transient ischemic attack, as well as hypertension.
Furthermore, this patient has a CHADS 2 score
(congestive HF, hypertension, age older than 75 years,
diabetes, and prior stroke of transient ischemic attack) of
3, so anticoagulation with warfarin to a goal INR of 2.5
is indicated.
5. Answer: A
With the new diagnosis of HF, H.D. can no longer
receive sotalol. Discontinuing this drug is very important
so that his risk of arrhythmic death is not increased.
Adding metoprolol is a reasonable approach at this time
to decrease his HR to less than 80 beats/minute, and
ß-blockade with bisoprolol, metoprolol, or carvedilol
is indicated with the new diagnosis of HF. There is no
indication for aspirin therapy in this patient, and his
anticoagulation is adequately managed with his INR
of 2.8 on warfarin therapy. If rhythm control is desired,
amiodarone and dofetilide are the only two drugs that
have been proven safe and effective in patients with
decreased EFs. However, amiodarone is not an attractive
option at this time because it is not clear whether his
AF symptoms are bothersome enough to warrant this
agent, which has several long-term adverse effects. The
drug interactions between amiodarone and digoxin and
warfarin would have to be addressed before initiating
amiodarone.
6. Answer: B
With his history of MI, D.W. has a compelling reason to
have a ß-blocker as part of his antihypertensive regimen.
In general, African Americans do not respond as well
as whites to the antihypertensive effects of ß-blockade;
however, it should still be used. The maintenance
of hydrochlorothiazide in his regimen increases the
likelihood of adequate BP control because African
Americans typically respond well to diuretic therapy,
bearing in mind that most individuals require two or
more drugs to attain adequate BP control. The regimens
without a ß-blocker are not appropriate because of
D.W.'s medical history. Therapy consisting of losartan
or diltiazem is inferior to ß-blockade in this patient
population.
 Outpatient Cardiology

goals have been achieved, such as a resting HR of 65-60

7. Answer: C beats/minute. The only available option that incorporates
The BP goal in individuals with diabetes mellitus or increased HR control with ß-blockade is Answer D,
chronic renal dysfunction is less than 130/80 mm Hg. which also incorporates standing nitrate therapy. Adding
Despite the categorization of prehypertension, the a nitrate by itself is not advisable because of the potential
presence of diabetes warrants immediate therapy to for reflex tachycardia in an individual who already has
attain a more aggressive goal BP of less than 130/80 a higher than desired HR. The addition of a nitrate
mm Hg than in the nondiabetic population. The presence (increased oxygen supply) and increased ß-blockade
of diabetes presents a compelling reason to include an (decreased oxygen demand) is the best option for this
ACE inhibitor in the absence of any contraindication. patient.
Lisinopril initiated at a low dose of 2.5 mg/day is
appropriate given her level of renal dysfunction and
mildly elevated BP. Angiotensin-converting enzyme
inhibitors are superior to ARBs in patients with diabetes,
so losartan is not an ideal agent to initiate at this time.
Likewise, no compelling indication is present for
using a ß-blocker in this patient; therefore, an atenolol-
based regimen is less desirable than the ACE inhibitor
regimen. In all situations, lifestyle modifications should
be emphasized to this patient.
8. Answer: C
Because the patient is post-MI, his BP goal is less than
130/80 mm Hg, which he has achieved. Therefore, no
decision must be made based on improved BP control.
Because he is post-MI, he has a compelling indication
for ß -blocker therapy, which he is already receiving. He
has not provided any information to indicate the need
for additional antianginal therapies, so the addition of
a calcium channel blocker is not necessary. He is taking
appropriate antiplatelet and cholesterol-lowering drugs
according to the requirements for individuals with CAD.
An ACE inhibitor is indicated in all patients with CAD
unless a contraindication exists. Ramipril is reasonable
to add to this patient's regimen, and discontinuing
hydrochlorothiazide may be desirable to minimize the
occurrence of hypotension. However, hydrochlorothiazide
could also be continued if the likelihood of hypotension
was thought to be low. Vitamin E therapy is not
recommended in patients with CAD because of the lack
of benefit in this patient population.
9. Answer: D
Both ß-blockers and calcium antagonists can be used
to achieve HR goals in patients with stable angina.
However, this patient has a compelling indication for
ß-blockade over calcium antagonism (status post-MI),
and the dose has room to be increased. Therefore,
replacing the ß-blocker with a non-dihydropyridine
calcium antagonist is not ideal. Although nitroglycerin
as needed can be used before exertion to minimize the
occurrence of angina, it should be used only after other

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 Outpatient Cardiology
ANSWERS AND EXPLANATIONS TO SELF-ASSESSMENT QUESTIONS
1. Answer: D
R.S. has LV systolic dysfunction, probably secondary to
her MI 4 months ago. Angiotensin-converting enzyme
inhibitors are considered the cornerstone of therapy for
LV systolic dysfunction based on evidence that they
slow the progression of HF and reduce symptoms,
hospitalizations, and mortality in this patient population.
Angiotensin-converting enzyme inhibitors should be
initiated in all patients with systolic dysfunction. This
patient does not have any contraindications for using an
ACE inhibitor. Digoxin is not indicated unless a patient
is symptomatic on optimal HF therapy. R.S. is neither
symptomatic nor on optimal therapy. ß-Blockers are
recommended, and R.S. is already taking a P-blocker
at the target dose. Thus, no rationale exists for adding
carvedilol.
2. Answer: C
J.O. is taking the target dose of enalapril, and further
increases in the enalapril dose are not necessary unless
the patient remains hypertensive once target doses of all
agents shown to reduce morbidity and mortality in HF
are reached. The addition of ß-blocker therapy, initially
at a low dose, together with ACE inhibitor therapy, is
recommended for further reductions in morbidity and
mortality and for slowing the progression of HF. Digoxin
is indicated only in symptomatic patients, despite
optimal therapy.
3. Answer: A
J.M. has diastolic dysfunction, which is a problem with
ventricular relaxation. The preferred therapy is either
a ß-blocker or a non-dihydropyridine calcium channel
blocker, both of which slow the HR and permit greater
time for the ventricle to fill with blood. Nifedipine can
cause reflex tachycardia, which potentiates diastolic
dysfunction by reducing ventricular filling time.
Diuretics should be used cautiously because patients with
diastolic dysfunction are often fluid-dependent (preload)
for maximal ventricular filling. In addition, J.M. has no
symptoms of systemic congestion, suggesting a need
for increased diuresis. Digoxin does not have a role in
managing diastolic dysfunction, and although ACE
inhibitors are first-line therapy for systolic dysfunction,
they can be considered in diastolic dysfunction if further
antihypertensive therapies are needed after the HR is
decreased.
© 2010 American College of Clinical Pharmacy
35
4. Answer: D
B.W. has two moderate risk factors (hypertension and
age older than 75) as well as a CHADS 2, score of 2,
making him a candidate for warfarin therapy because
of his AF. This will greatly decrease his risk of stroke
from about 5% per year to about 1% per year. Because
his HR is much less than 80 beats/minute with the
atenolol therapy, there is no reason to discontinue this,
nor is there a reason to add an additional rate control
drug, such as digoxin or diltiazem. With his peripheral
vascular disease, atorvastatin therapy is necessary,
and his BP is well controlled; therefore, increasing
the lisinopril dose is not warranted. To derive the
beneficial antiplatelet effects for cardiovascular event
prevention, 81 mg of aspirin is adequate. Aspirin 325
mg is also effective but has a greater risk of bleeding
with concomitant warfarin.
5. Answer: A
Z.G. is experiencing a rapid ventricular response with
exercise/strenuous activity, causing the sensation of
palpitations and dyspnea. Digoxin alone exhibits poor
control of the ventricular rate during times of high
sympathetic influence (e.g., exercise). It is common
to require additional therapy to control the ventricular
rate adequately. A ß-blocker such as atenolol is a good
choice to maintain HR during activity. Better agents than
verapamil exist because of verapamil's drug interaction
with digoxin. The subsequent digoxin concentration
may cause symptoms of toxicity. Similarly, doubling
the digoxin dose would about double the current serum
concentration to 2.2 ng/dL, which should be avoided.
Instructing the patient to avoid activity is not desirable
because physical activity should be encouraged and
supported in all patients, especially in those with risk
factors for cardiovascular disease.
6. Answer: B
R.P.'s BP goal is less than 130/80 mm Hg. His therapy
with nifedipine is likely highly effective; however,
additional therapy is necessary to achieve his goal BP.
Ideally, a low-dose diuretic could be added. However,
his history of gout makes hydrochlorothiazide a less
attractive option, especially at such a large dose (50
mg). Angiotensin-converting enzyme inhibitors are the
drug of choice for patients with a history of stroke, and
ramipril is a reasonable selection in this patient, whose
history includes a transient ischemic attack. An initial
dose of 2.5 mg is reasonable in this elderly man. No
 Outpatient Cardiology

indications are present in R.P. to suggest the need for be ideal and might even worsen his angina symptoms
a ß -blocker or a non-dihydropyridine calcium channel because of a relative tachycardia, despite the increased
blocker. myocardial oxygen supply. Adding amlodipine to the
existing HR control therapy is the best choice because
7. Answer: C it optimizes the oxygen supply, which has not yet been
During pregnancy, ACE inhibitors and ARBs are pharmacologically addressed. Adding antiplatelet
contraindicated because of associations with fetal growth therapy with clopidogrel or increasing therapy for
restriction, neonatal renal failure, skeletal abnormalities, dyslipidemia will not affect his acute angina symptoms.
and fetal death. Methyldopa is preferred as first-line
therapy for hypertension in pregnancy based on reports of
stable uteroplacental bloodflow and fetal hemodynamics
during methyldopa therapy, and there is no evidence
of long-term adverse effects on child development. In
addition, hydralazine is considered safe in pregnancy;
however, the ACE inhibitor should be discontinued for
this option to be a reasonable alternative.
8. Answer: D
The proportion of patients receiving Trillionapril who
have an event will be compared with the proportion
of patients receiving enalapril who have an event.
The best statistical test for comparing two proportions
(count data) is chi-square analysis. Chi-square analysis
is appropriate to analyze nominal or categorical data.
An analysis of variance is appropriate when there are
more than two treatment groups. The Student unpaired
t-test is for continuous data. The Mann-Whitney U-test
is appropriate for continuous data that are not normally
distributed.
9. Answer: C
This patient has newly diagnosed CAD. All patients with
CAD should be taking at least aspirin, lipid-lowering
therapy to a goal of less than 100 mg/dL, and an ACE
inhibitor. This patient is already receiving appropriate
antiplatelet therapy, and the proposed modifications to
his lipid-lowering regimen appear reasonable to reach
an LDL-C concentration of less than 100 mg/dL. The
other lipid-lowering regimens offered are not obviously
better at reaching the stated goal. An ACE inhibitor is
missing from this patient's discharge regimen, so the
addition of ramipril is warranted. A ß-blocker is not
required because no myocardial damage (infarction) has
occurred. However, if additional BP lowering is required,
a ß-blocker is a reasonable choice because the patient is
at high risk of future cardiovascular events.
10. Answer: A
R.K. appears to have sufficient HR control, both at
rest and with exercise, so it is desirable to continue his
ß-blocker therapy. Discontinuing his atenolol and adding
nifedipine, which is devoid of HR effects, would not

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